title: Assessment of ocular surface toxicity after topical instillation of nitric oxide donors.
abstract: OBJECTIVE
  To evaluate the ocular surface toxicity of two nitric oxide donors in ex vivo and in vivo animal models: S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) in a hydroxypropyl methylcellulose (HPMC) matrix at final concentrations 1.0 and 10.0 mM.
  
  
  METHODS
  Ex vivo GSNO and SNAC toxicities were clinically and histologically analyzed using freshly excised pig eyeballs. In vivo experiments were performed with 20 albino rabbits which were randomized into 4 groups (5 animals each): Groups 1 and 2 received instillations of 150 µL of aqueous HPMC solution containing GSNO 1.0 and 10.0 mM, respectively, in one of the eyes; Groups 3 and 4 received instillations of 150 µL of aqueous HPMC solution-containing SNAC 1.0 and 10.0 mM, respectively, in one of the eyes. The contralateral eyes in each group received aqueous HPMC as a control. All animals underwent clinical evaluation on a slit lamp and the eyes were scored according to a modified Draize eye test and were histologically analyzed.
  
  
  RESULTS
  Pig eyeballs showed no signs of perforation, erosion, corneal opacity or other gross damage. These findings were confirmed by histological analysis. There was no difference between control and treated rabbit eyes according to the Draize eye test score in all groups (p>0.05). All formulations showed a mean score under 1 and were classified as "non-irritating". There was no evidence of tissue toxicity in the histological analysis in all animals.
  
  
  CONCLUSIONS
  Aqueous HPMC solutions containing GSNO and SNAC at concentrations up to 10.0 mM do not induce ocular irritation.
authors.affiliation: Department of Ophthalmology, Universidade Federal de São Paulo, São Paulo, SP, Brazil. angelino@sadalla.com.br
authors.forename: Angelino Julio
authors.initials: AJ
authors.lastname: Cariello
authors.forename: Gabriela Freitas Pereira de
authors.initials: GF
authors.lastname: Souza
authors.forename: Márcia Serva
authors.initials: MS
authors.lastname: Lowen
authors.forename: Marcelo Ganzarolli de
authors.initials: MG
authors.lastname: Oliveira
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: Höfling-Lima
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005123:Eye / Q000187:drug effects* / Q000473:pathology; D007322:Instillation, Drug; D008297:Male; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000633:toxicity*; D011817:Rabbits; D011897:Random Allocation; D026422:S-Nitrosoglutathione / Q000008:administration & dosage / Q000633:toxicity*; D013552:Swine
chemical_list: D020030:Nitric Oxide Donors; C024940:S-nitroso-N-acetylcysteine; D026422:S-Nitrosoglutathione; D000111:Acetylcysteine